Microneedle array patches having polymeric microneedles and methods for using the same
The microneedle array patch with a polymeric structure and pressure plate design addresses the inefficiencies of existing technologies by enabling pain-free and efficient collection of biological samples, achieving a significant increase in sample collection rates.
Patent Information
- Application Number
- PCT/US2025/032264
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2024-06-07
- Filing Date
- 2025-06-04
- Publication Date
- 2025-12-11
AI Technical Summary
Existing microneedle technologies for intradermal drug delivery and diagnostics are invasive, painful, and inefficient in collecting biological samples like dermal fluid, lacking a reliable and minimally invasive method for targeted delivery and sampling.
A microneedle array patch with a polymeric structure and pressure plate design that allows pain-free puncturing of the skin for collecting biological fluids, utilizing an array of polymeric microneedles and a pressure plate with configured holes to collect interstitial fluid efficiently.
The microneedle array patch enables rapid, reproducible, and minimally invasive collection of biological samples, increasing the collection rate by up to 10-fold, providing a reliable alternative to traditional methods without causing skin irritation.
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Figure US2025032264_11122025_PF_FP_ABST
Abstract
Description
[0001]Attorney Docket No.: STAN-2203WO Stanford No.: S24-200 MICRONEEDLE ARRAY PATCHES HAVING POLYMERIC MICRONEEDLES AND METHODS FOR USING THE SAME CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Patent Application No. 63 / 657,346, filed on June 7, 2024, which application is incorporated herein by reference in its entirety. GOVERNMENT RIGHTS This invention was made with Government support under contract CA009695 awarded by the National Institutes of Health. The Government has certain rights in the invention. INTRODUCTION The intradermal (ID) space has been actively explored as a means for drug delivery and diagnostics that are minimally invasive. Intradermal drug delivery is the process of delivering formulations into layers of skin. ID access necessitates puncturing the outermost layer of skin called the stratum corneum (StC), a tough barrier that provides mechanical integrity for the skin. Human skin is a complex, multi-layer organ, that includes the stratum corneum, epidermis, dermis and hypodermis. Often, these treatments target either the epidermal or dermal layers of skin, which are situated above blood vessels and nerve fibers of the skin. It offers an attractive alternative to intravenous (IV) injection, which often elicits systemic effects and can be particularly advantageous for targeted, local drug delivery. ID drug delivery can provide for the ability to deliver compounds with a significant first-pass effect, or metabolization by the liver which can prematurely degrade the therapeutic compound, upon systemic administration. Further, ID access also reduces pain associated with hypodermic injections and can help eliminate the risk of transmitting blood-borne diseases through the generation of dangerous medical waste. ID access can also be self-administered and can eliminate reliance on trained medical professionals. Microneedles or microneedle patches or Micro-Array Patches (MAPs) have a series of micrometer-sized projections that can painlessly puncture the skin and access Attorney Docket No.: STAN-2203WO Stanford No.: S24-200 the epidermal / dermal layer and facilitate sampling of interstitial fluid. MAPs are employed in cosmetics, such as for use in treating acne scars and stretch marks by penetrating the stratum corneum to create micro conduits that stimulate growth factor secretion and collagen production. Microneedles are conventionally solid or hollow microneedles that are micro-molded from templates and fabricated by a three-step process master fabrication, mold fabrication and mold filling to generate hollow, metallic projections with uniform geometries. Microneedles have been generally manufactured to be produced in a manner like conventional hypodermic needles. SUMMARY Aspects of the present disclosure include a microneedle array patch. Patches according to certain embodiments include a polymeric structure having an array of polymeric microneedles configured to puncture the skin of a subject and a pressure plate having an array of holes configured for collecting a biological fluid sample from each skin puncture site by the array of polymeric microneedles. In some instances, the array of holes of the pressure plate is configured for insertion of the polymeric microneedles therethrough, such as where the polymeric microneedles are punctured into the skin of the subject, retracted from the skin back through the array of holes and pressure is applied to the pressure plate onto the skin surface to collect the biological fluid sample from each skin puncture site. Methods for using the microneedle array patch to collect a biological fluid sample (e.g., interstitial fluid) from a subject are also described. Kits having one or more of the subject microneedle array patches are also described. In some embodiments, the array of holes of the pressure plate is configured for insertion of the polymeric microneedles therethrough. In some instances, the pressure plate has a planar surface (e.g., flat surface). In some instances, the pressure plate has a concave surface. In some instances, the pressure plate has a convex surface. In certain instances, the pressure plate has a surface that matches the skin curvature of the subject. In certain instances, the pressure plate has a shape-conforming surface. In some embodiments, the polymeric structure having the array of polymeric microneedles is integrated together with the pressure plate. In some embodiments, the surface of the pressure plate includes a wall which extends from one or more of the array of holes, such as from each of the holes in the Attorney Docket No.: STAN-2203WO Stanford No.: S24-200 array. In some instances, the walls are configured for insertion into each puncture site formed by the array of polymeric microneedles. In some instances, the pressure plate includes a reservoir for the collected biological fluid sample. In some instances, the collected biological fluid sample fills the holes of the array. In some embodiments, the biological fluid is interstitial fluid. In some instances, the biological fluid is dermal fluid. In some instances, the pressure plate includes one or more hydrophilic surfaces. In some instances, the array of holes has a hydrophilic surface. In some instances, the reservoir for collecting the biological fluid sample has a hydrophilic surface. In some instances, the one or more walls which extend from the holes have a hydrophilic surface. In some instances, the holes of the pressure plate have a circular cross-section. In some instances, the holes of the pressure plate have an oval cross-section. In some instances, the holes of the pressure plate have a polygonal cross-section, such as where the holes have a square cross-section, a triangular cross-section, a rectangular cross- section, a pentagonal cross-section or a hexagonal cross-section. The size of the holes may have a width (or diameter when the holes are circular) of from 200 µm to 750 µm, such as from 300 µm to 675 µm. In some instances, the pressure plate has a height of from 300 µm to 2000 µm, such as from 500 µm to 1500 µm. In some instances, the depth of each hole is from 300 µm to 2000 µm, such as from 500 µm to 1500 µm. In some embodiments, each hole of the pressure plate has a volume of from 0.1 µL to 100 µL, such as a volume of from 2 µL to 25 µL. In some embodiments, each polymeric microneedle has a beveled tip. In some instances, each polymeric microneedle has a lattice structure. In some instances, the lattice structure has 2 or more repeating lattice cell units. In some instances, the lattice cell unit has a lattice shape such as tetrahedral, Kagome, rhombic, icosahedral, Voronoi and triangular. In some instances, each polymeric microneedle has a width of from 200 µm to 750 µm, such as from 250 µm to 500 µm. In some instances, each polymeric microneedle has a length of from 300 µm to 3000 µm, such as from 500 µm to 1000 µm. In some instances, the polymeric microneedle has a hollow internal space. In some instances, each polymeric microneedle includes a tip section, a body section and a base section. In some instances, one or more of the polymeric has a tip section having a lattice structure, a body section having a hollow structure; and a base section having a solid structure. In some instances, each polymeric microneedle has a tip section that Attorney Docket No.: STAN-2203WO Stanford No.: S24-200 has a length of from 25 µm to 500 µm. In some instances, the tip section has a base width of 50 µm to 300 µm. In some instances, each polymeric microneedle has a tip diameter of from 0.1 µm to 10 µm. In some instances, each polymeric microneedle has a body section that has a length of from 50 µm to 1000 µm. In some instances, the body section has a width of 50 µm to 300 µm. In some instances, each polymeric microneedle has a base section that has a length of from 25 µm to 500 µm. In some instances, the base section has a base width of 50 µm to 300 µm. In some instances, each polymeric microneedle has a volume of from 0.01 µL to 2 µL. In some instances, the polymeric structure is formed from one or more polymerizable materials. In some instances, the polymeric structure is formed from two or more different polymerizable materials. In some instances, each polymerizable material is selected from polycaprolactone, polyglycolic acid, polylactic acid, polylactic-co-glycolic acid, polyethylene glycol, polyethylene glycol dimethacrylate (PEGDMA), thiol-enes, anhydrides, polyacrylic acid, poly methylmethacrylate, trimethylolpropane triacrylate (TMPTA) monomer, polyvinyl alcohol, polyvinylpyrrolidone, vinyl carbonates, vinyl esters, acrylamides, hyaluronic acid, chitosan, collagen, gelatin, carboxymethylcellulose, and blends or copolymers thereof. In some instances, the polymerizable material includes carbon nanotubes. Aspects of the present disclosure also include methods for collecting a biological fluid sample from a subject with a microneedle array patch. In practicing methods according to certain embodiments, the skin surface of a subject is punctured with polymeric structure having an array of polymeric microneedles and collecting a biological fluid sample from each skin puncture site into an array of holes of a pressure plate. In some instances, the method includes positioning the pressure plate on the surface of the skin of the subject and puncturing the skin surface by inserting the array of polymeric microneedles through the array of holes of the pressure plate. In some instances, the method includes retracting the array of microneedles from the skin surface. In some instances, the array of microneedles is inserted into the skin surface and retracted immediately after puncturing the skin surface. In other instances, the array of microneedles is inserted into the skin surface and maintained in the skin of the subject for 30 seconds or more, such as 1 minute or more and including for 10 minutes or more. Attorney Docket No.: STAN-2203WO Stanford No.: S24-200 In some instances, the array of microneedles is inserted into the skin surface and maintained in the skin of the subject for a period of time of from 1 minute to 30 minutes. In some instances, the method includes collecting interstitial fluid from the skin of the subject into the holes of the array of the pressure plate. In some instances, the method includes collecting dermal fluid from the skin of the subject into the holes of the array of the pressure plate. In certain instances, the pressure plate applied to the skin surface of the subject to collect biological fluid sample into the holes of the array and maintained in contact with the subject for an extended period of time, such as for 1 minute or more, such as 5 minutes or more and including for 10 minutes or more. In some instances, the pressure plate is maintained in contact with the skin (e.g., by applying pressure to the skin of the subject with the pressure plate) for 30 minutes or longer. In certain instances, the pressure plate applied to the skin surface of the subject and removed within 15 minutes or less, such as within 5 minutes or less and including within 1 minute or less. In some instances, the biological fluid sample is collected at a rate of from 1 µL to 10 µL per minute, such as from 5 µL to 20 µL in 20 minutes. BRIEF DESCRIPTION OF THE FIGURES The invention may be best understood from the following detailed description when read in conjunction with the accompanying drawings. Included in the drawings are the following figures: FIG.1 depicts a polymeric structure having an array of polymeric microneedles of a microneedle array patch according to certain embodiments. FIG.2 depicts pressure plates with holes having different lengths and cross- sections according to certain embodiments. FIG.3 depicts a pressure plate having walls which extends from the surface of the pressure plate according to certain embodiments. FIG.4 depicts pressure plates having an array of holes configured for collecting a biological fluid sample from each skin puncture site by the array of polymeric microneedles according to certain embodiments. FIG.5 depicts an integrated one-part microneedle array system according to certain embodiments. Attorney Docket No.: STAN-2203WO Stanford No.: S24-200 FIG.6 depicts collecting a biological fluid (e.g., interstitial fluid) with a microneedle array patch according to certain embodiments. DETAILED DESCRIPTION Aspects of the present disclosure include a microneedle array patch. Patches according to certain embodiments include a polymeric structure having an array of polymeric microneedles configured to puncture the skin of a subject and a pressure plate having an array of holes configured for collecting a biological fluid sample from each skin puncture site by the array of polymeric microneedles. In some instances, the array of holes of the pressure plate is configured for insertion of the polymeric microneedles therethrough, such as where the polymeric microneedles are punctured into the skin of the subject, retracted from the skin back through the array of holes and pressure is applied to the pressure plate onto the skin surface to collect the biological fluid sample from each skin puncture site. Methods for using the microneedle array patch to collect a biological fluid sample (e.g., interstitial fluid) from a subject are also described. Kits having one or more of the subject microneedle array patches are also described. Before the present invention is described in greater detail, it is to be understood that this invention is not limited to particular embodiments described, as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting, since the scope of the present invention will be limited only by the appended claims. Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limit of that range and any other stated or intervening value in that stated range, is encompassed within the invention. The upper and lower limits of these smaller ranges may independently be included in the smaller ranges and are also encompassed within the invention, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the invention. Certain ranges are presented herein with numerical values being preceded by the term "about." The term "about" is used herein to provide literal support for the exact Attorney Docket No.: STAN-2203WO Stanford No.: S24-200 number that it precedes, as well as a number that is near to or approximately the number that the term precedes. In determining whether a number is near to or approximately a specifically recited number, the near or approximating unrecited number may be a number which, in the context in which it is presented, provides the substantial equivalent of the specifically recited number. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although any methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the present invention, representative illustrative methods and materials are now described. All publications and patents cited in this specification are herein incorporated by reference as if each individual publication or patent were specifically and individually indicated to be incorporated by reference and are incorporated herein by reference to disclose and describe the methods and / or materials in connection with which the publications are cited. The citation of any publication is for its disclosure prior to the filing date and should not be construed as an admission that the present invention is not entitled to antedate such publication by virtue of prior invention. Further, the dates of publication provided may be different from the actual publication dates which may need to be independently confirmed. It is noted that, as used herein and in the appended claims, the singular forms “a”, “an”, and “the” include plural referents unless the context clearly dictates otherwise. It is further noted that the claims may be drafted to exclude any optional element. As such, this statement is intended to serve as antecedent basis for use of such exclusive terminology as “solely,” “only” and the like in connection with the recitation of claim elements, or use of a “negative” limitation. As will be apparent to those of skill in the art upon reading this disclosure, each of the individual embodiments described and illustrated herein has discrete components and features which may be readily separated from or combined with the features of any of the other several embodiments without departing from the scope or spirit of the present invention. Any recited method can be carried out in the order of events recited or in any other order which is logically possible. Attorney Docket No.: STAN-2203WO Stanford No.: S24-200 While the apparatus and method has or will be described for the sake of grammatical fluidity with functional explanations, it is to be expressly understood that the claims, unless expressly formulated under 35 U.S.C. §112, are not to be construed as necessarily limited in any way by the construction of "means" or "steps" limitations, but are to be accorded the full scope of the meaning and equivalents of the definition provided by the claims under the judicial doctrine of equivalents, and in the case where the claims are expressly formulated under 35 U.S.C. §112 are to be accorded full statutory equivalents under 35 U.S.C. §112. MICRONEEDLE ARRAY PATCHES Aspects of the present disclosure include a microneedle array patch. In some embodiments, the microneedle array patch is configured for collecting a biological specimen from a subject, such as dermal fluid or interstitial fluid. In some instances, the microneedle array patch provides for pain-free collection of a biological sample. In some instances, the microneedle array patch provides for collecting the biological sample from the subject without causing irritation to the puncture sites (e.g., on the skin surface). Dermal interstitial fluid (ISF) is a useful diagnostic specimen that contains novel biomarkers and offers an alternative to phlebotomy. The microneedle array patches described herein provide a reproducible, consistent and minimally invasive collection method that can reliably retrieve useful volumes of ISF quickly, increasing the rate of sample collection by 25% or more, such as by 50% or more, such as by 75% or more, such as by 90% or more, such as by 2-fold or more, such as by 5-fold or more and including by 10-fold or more. As described below, the subject microneedle array patches according to certain embodiments have an optimized geometry to produce a distribution of pressure gradient in the skin that maximizes the flow of ISF to the collection sites. Patches according to certain embodiments include a polymeric structure having an array of polymeric microneedles configured to puncture the skin of a subject and a pressure plate having an array of holes configured for collecting a biological fluid sample from each skin puncture site by the array of polymeric microneedles. In embodiments, polymeric structures include one or more polymeric microneedles. In some instances, the polymeric structure includes a plurality of microneedles, such as 2 or more polymeric Attorney Docket No.: STAN-2203WO Stanford No.: S24-200 microneedles, such as 3 or more, such as 4 or more, such as 5 or more, such as 10 or more, such as 25 or more, such as 50 or more, such as 100 or more, such as 250 or more, such as 500 or more and including 1000 polymeric microneedles or more. In some instances, the polymeric structure includes an array of polymeric microneedles. In some instances, the polymeric microneedles or the array are arranged in one or more lines. For example, the polymeric microneedles may be positioned along 2 or more parallel lines, such as 3 or more, such as 4 or more, such as 5 or more, such as 6 or more, such as 7 or more, such as 8 or more, such as 9 or more, such as 10 or more, such as 15 or more, such as 20 or more and including 25 or more parallel lines of microneedles. In certain instances, the polymeric microneedles are arranged into a geometric configuration, where arrangements of interest include, but are not limited to a square configuration, rectangular configuration, trapezoidal configuration, triangular configuration, hexagonal configuration, heptagonal configuration, octagonal configuration, nonagonal configuration, decagonal configuration, dodecagonal configuration, circular configuration, oval configuration as well as irregular shaped configurations. In certain instances, the polymeric microneedles are arranged in a random configuration. In some embodiments, the microneedles are separated from each other on the polymeric structure by an average distance of from 1 µm to 1000 µm, such as from 2 µm to 950 µm, such as from 3 µm to 900 µm, such as from 4 µm to 850 µm, such as from 5 µm to 800 µm, such as from 6 µm to 750 µm, such as from 7 µm to 700 µm, such as from 8 µm to 650 µm, such as from 9 µm to 600 µm, such as from 10 µm to 550 µm, such as from 15 µm to 500 µm, such as from 20 µm to 450 µm and including from 25 µm to 400 µm. The plurality of polymeric microneedles may each be the same size or patches may include plurality of polymeric microneedles having different sizes. Each polymeric microneedle independently may have a length of from 50 µm to 2000 µm, such as from 75 µm to 1950 µm, such as from 100 µm to 1900 µm, such as from 125 µm to 1850 µm, such as from 150 µm to 1800 µm, such as from 175 µm to 1750 µm, such as from 200 µm to 1700 µm, such as from 225 µm to 1650 µm, such as from 250 µm to 1600 µm, such as from 275 µm to 1550 µm and including from 300 µm to 1500 µm. Each polymeric microneedle independently may have a width (diameter when the polymeric microneedle has a circular cross-section) of from 50 µm to 1000 µm, such as Attorney Docket No.: STAN-2203WO Stanford No.: S24-200 from 75 µm to 950 µm, such as from 100 µm to 900 µm, such as from 125 µm to 850 µm, such as from 150 µm to 800 µm, such as from 175 µm to 750 µm, such as from 200 µm to 700 µm, such as from 225 µm to 650 µm, such as from 250 µm to 600 µm, such as from 275 µm to 550 µm and including from 300 µm to 500 µm. In some embodiments, polymeric microneedles described herein have a lattice microstructure. In some instances, the lattice microstructures of the polymeric microneedles described herein have 2 or more repeating lattice cell units, such as 3 or more repeating lattice cell units, such as 4 or more repeating lattice cell units and including 5 or more repeating lattice cell units. In some instances, the lattice microstructure has a lattice shape selected from tetrahedral, Kagome, rhombic, icosahedral, Voronoi or triangular. In some instances, the lattice microstructure is composed of two or more lattice cell units having different lattice shapes, such where the lattice microstructure is composed of 3 or more different lattice shapes, such as 4 or more different lattice shapes and including where the lattice microstructure is composed of 5 or more different lattice shapes. In some embodiments, the lattice microstructure is formed from lattice cells having a unit size of from 1 µm to 1000 µm, such as from 5 µm to 950 µm, such as from 10 µm to 900 µm, such as from 15 µm to 850 µm, such as from 20 µm to 800 µm, such as from 25 µm to 750 µm, such as from 30 µm to 700 µm, such as from 35 µm to 650 µm, such as from 40 µm to 600 µm, such as from 45 µm to 550 µm and including from 50 µm to 500 µm, for example from 200 µm to 500 µm. In embodiments, the lattice microstructure has a volume of from 0.01 µL to 25 µL, such as from 0.02 µL to 24.5 µL, such as from 0.03 µL to 24 µL, such as from 0.04 µL to 23.5 µL, such as rom 0.05 µL to 23 µL, such as from 0.6 µL to 22.5 µL, such as from 0.07 µL to 22 µL, such as from 0.08 µL to 21.5 µL, such as from 0.09 µL to 21 µL, such as from 0.1 µL to 20 µL, such as from 0.5 µL to 19 µL, such as from 1 µL to 18 µL, such as from 2 µL to 17 µL, such as from 3 µL to 16 µL and including from 4 µL to 15 µL. In some embodiments, the density of lattice cell units remains constant throughout the lattice microstructure of polymeric structures of interest. In some instances, lattice microstructures have different densities of lattice cell units. In some instances, polymeric microneedles have a low density of lattice cell units, a medium density of lattice cell units and a high density of lattice cell units. In other embodiments, Attorney Docket No.: STAN-2203WO Stanford No.: S24-200 the density of lattice cell units varies at one or more parts of the lattice microstructure. In some embodiments, the lattice microstructure contains regions of increased lattice cell density, such as where the lattice cell density in these regions is increased by 1% or more across the longitudinal axis of the lattice microstructure, such as by 2% or more, such as by 3% or more, such as by 4% or more, such as by 5% or more, such as by 10% or more, such as by 20% or more, such as by 30% or more, such as by 40% or more and including by 50% or more. In some instances, the regions of increased lattice cell density are present at various increments across the longitudinal axis of the lattice microstructure. For example, the regions of increased lattice cell density may be present at increments of every 10 µm or more across the longitudinal axis of the lattice microstructure, such as every 20 µm or more, such as every 30 µm or more, such as every 40 µm or more and including every 50 µm or more. In some instances, lattice microstructures have a gradient in the density of lattice cell units according to certain embodiments. In some instances, the density of lattice cell units exhibits a gradient in one or more parts of the lattice microstructure. In certain instances, the density of lattice cell units gradually increases across a longitudinal axis of the lattice microstructure. For example, the density of the lattice cell units may increase by 1% or more across the longitudinal axis of the lattice microstructure, such as by 2% or more, such as by 3% or more, such as by 4% or more, such as by 5% or more, such as by 10% or more, such as by 20% or more, such as by 30% or more, such as by 40% or more and including by 50% or more. In some embodiments, the density of the lattice cell units increases at predetermined increments across the longitudinal axis of the lattice microstructure, such as where the density of the lattice cell units increases every 1% or more of the length across the longitudinal axis of the lattice microstructure, such as every 2% or more, such as every 3% or more, such as every 4% or more, such as every 5% or more, such as every 6% or more, such as every 7% or more, such as every 8% or more, such as every 9% or more and including every 10% or more. Depending on the size of the lattice microstructure, the density of the lattice cell units may increase every 1 µm or more across the longitudinal axis, such as every 2 µm or more, such as every 3 µm or more, such as every 4 µm or more, such as every 5 µm or more, such as every 10 µm or more, such as every 20 µm or more, such as every 30 µm or more, such as every 40 µm or Attorney Docket No.: STAN-2203WO Stanford No.: S24-200 more and including every 50 µm or more. For example, the density of the lattice cell units may increase by 1% or more every 25 µm or more across the longitudinal axis of the lattice microstructure, such as by 2% or more every 25 µm or more across the longitudinal axis of the lattice microstructure, such as 5% or more every 25 µm or more across the longitudinal axis of the lattice microstructure. In some embodiments, the lattice microstructure includes a plurality of struts. Struts according to certain embodiments provide mechanical integrity to the lattice microstructure. In some instances, struts have a thickness which range from 1 µm to 200 µm, such as from 2 µm to 190 µm, such as from 3 µm to 180 µm, such as from 4 µm to 170 µm, such as from 5 µm to 160 µm, such as from 6 µm to 150 µm, such as from 7 µm to 140 µm, such as from 8 µm to 130 µm, such as from 9 µm to 120 µm and including from 10 µm to 100 µm. For instance, the strut size may be in certain examples from 50 µm to 100 µm such as 70 µm to 90 µm. (see e.g., Figure 3A) In some instances, the lattice microstructures exhibit a mechanical integrity sufficient to be load bearing, such as for example, as a polymeric microneedle (as described below) that can be administered to a subject. Depending on the density of the lattice microstructure, in some embodiments polymeric structures exhibit a mechanical integrity sufficient to carry a load of 0.1 N or more, such as 0.5 N or more, such as 1 N or more, such as 2 N or more, such as 3 N or more, such as 4 N or more, such as 5 N or more, such as 10 N or more, such as 15 N or more, such as 20 N or more, such as 25 N or more, such as 50 N or more, such as 75 N or more and including 100 N or more. In some embodiments, the lattice microstructure includes one or more structural support struts which is positioned within the lattice microstructure to provide increased mechanical integrity, such as where the mechanical integrity is increased by 5% or more, such as by 25% or more and including by 75% or more. For example, the structural support struts may increase the load that the lattice microstructure can carry by 0.5 N or more, such as by 1 N or more, such as by 5 N or more, such as by 10 N or more, such as by 25 N or more, such as by 50 N or more and including by 100 N or more. In some instances, the structural support struts are positioned within the interior of the lattice microstructure. In other embodiments, the support struts are positioned along the exterior of the lattice microstructure. In some instances, the polymeric microneedles are compliant and exhibit a flexible integrity. In some instances, the polymeric Attorney Docket No.: STAN-2203WO Stanford No.: S24-200 microneedles yield under a load bearing. As described above, in some embodiments, the polymeric microneedles may exhibit elastic deformation. Polymeric microneedles may be any three-dimensional geometric shape including but are not limited to: rectilinear cross sectional shapes, e.g., squares, rectangles, trapezoids, triangles, hexagons, etc., curvilinear cross-sectional shapes, e.g., circles, ovals, etc., as well as irregular shapes, e.g., a parabolic bottom portion coupled to a planar top portion. Polymeric structures having a lattice microstructure of interest may have a length of from 50 µm to 2000 µm, such as from 75 µm to 1950 µm, such as from 100 µm to 1900 µm, such as from 125 µm to 1850 µm, such as from 150 µm to 1800 µm, such as from 175 µm to 1750 µm, such as from 200 µm to 1700 µm, such as from 225 µm to 1650 µm, such as from 250 µm to 1600 µm, such as from 275 µm to 1550 µm and including from 300 µm to 1500 µm. Polymeric structures having a lattice microstructure of interest may have a width of from 50 µm to 1000 µm, such as from 75 µm to 950 µm, such as from 100 µm to 900 µm, such as from 125 µm to 850 µm, such as from 150 µm to 800 µm, such as from 175 µm to 750 µm, such as from 200 µm to 700 µm, such as from 225 µm to 650 µm, such as from 250 µm to 600 µm, such as from 275 µm to 550 µm and including from 300 µm to 500 µm. In embodiments, the polymeric structure is formed from a polymerizable material which may include but is not limited to polycaprolactone, polyglycolic acid, polylactic acid, polylactic-co-glycolic acid, polyethylene glycol, thiol-enes, anhydrides, polyacrylic acid, poly methylmethacrylate, polyvinyl alcohol, polyvinylpyrrolidone, vinyl carbonates, vinyl esters, acrylamides, hyaluronic acid, chitosan, collagen, gelatin, carboxymethylcellulose, and blends or copolymers thereof. In certain embodiments, the polymeric structure is formed from polyethylene glycol dimethacrylate (PEGDMA). In certain embodiments, the polymeric structure is formed from trimethylolpropane triacrylate (TMPTA) monomer. In certain embodiments, the polymerizable material is selected from polycarbonates, polyvinyl chloride (PVC), polyurethanes, polyethers, polyamides, polyimides, or copolymers of these thermoplastics, such as PETG (glycol- modified polyethylene terephthalate), among other polymeric plastic materials. In certain embodiments, the beamsplitter is formed from a polyester, where polyesters of interest may include, but are not limited to, poly(alkylene terephthalates) such as poly(ethylene terephthalate) (PET), bottle-grade PET (a copolymer made based on monoethylene Attorney Docket No.: STAN-2203WO Stanford No.: S24-200 glycol, terephthalic acid, and other comonomers such as isophthalic acid, cyclohexene dimethanol, etc.), poly(butylene terephthalate) (PBT), and poly(hexamethylene terephthalate); poly(alkylene adipates) such as poly(ethylene adipate), poly(1,4-butylene adipate), and poly(hexamethylene adipate); poly(alkylene suberates) such as poly(ethylene suberate); poly(alkylene sebacates) such as poly(ethylene sebacate); poly(ε-caprolactone) and poly(β-propiolactone); poly(alkylene isophthalates) such as poly(ethylene isophthalate); poly(alkylene 2,6-naphthalene-dicarboxylates) such as poly(ethylene 2,6-naphthalene-dicarboxylate); poly(alkylene sulfonyl-4,4′-dibenzoates) such as poly(ethylene sulfonyl-4,4′-dibenzoate); poly(p-phenylene alkylene dicarboxylates) such as poly(p-phenylene ethylene dicarboxylates); poly(trans-1,4- cyclohexanediyl alkylene dicarboxylates) such as poly(trans-1,4-cyclohexanediyl ethylene dicarboxylate); poly(1,4-cyclohexane-dimethylene alkylene dicarboxylates) such as poly(1,4-cyclohexane-dimethylene ethylene dicarboxylate); poly([2.2.2]- bicyclooctane-1,4-dimethylene alkylene dicarboxylates) such as poly([2.2.2]- bicyclooctane-1,4-dimethylene ethylene dicarboxylate); lactic acid polymers and copolymers such as (S)-polylactide, (R,S)-polylactide, poly(tetramethylglycolide), and poly(lactide-co-glycolide); and polycarbonates of bisphenol A, 3,3′-dimethylbisphenol A, 3,3′,5,5′-tetrachlorobisphenol A, 3,3′,5,5′-tetramethylbisphenol A; polyamides such as poly(p-phenylene terephthalamide); polyethylene Terephthalate (e.g., MylarTM Polyethylene Terephthalate), combinations thereof, and the like. In some embodiments, the microneedle includes a tip section, a body section and a base section. In embodiments, one or more of the tip section, body section and base section of the polymeric microneedle have a lattice microstructure as described above. In some instances, one or more of the tip section, body section and base section have a solid structure (i.e., interior space that is completely filled). In some instances, one or more of the tip section, body section and base section have a hollow interior space. In certain embodiments, the microneedle includes a tip section having a solid structure, a body section having a lattice microstructure and a base section having a solid structure. In embodiments, the tip section may be a length of from 10 µm to 500 µm, such as from 20 µm to 490 µm, such as from 30 µm to 480 µm, such as from 40 µm to 470 µm, such as from 50 µm to 460 µm, such as from 60 µm to 450 µm, such as from 70 µm to 440 µm, such as from 80 µm to 430 µm, such as from 90 µm to 420 µm, such Attorney Docket No.: STAN-2203WO Stanford No.: S24-200 as from 100 µm to 410 µm, such as from 110 µm to 400 µm, such as from 120 µm to 390 µm, such as from 130 µm to 380 µm, such as from 140 µm to 370 µm and including from 150 µm to 360 µm. In some instances, the microneedle has a tip diameter of from 0.1 µm to 10 µm, such as from 0.5 µm to 9 µm, such as from 1 µm to 8 µm and including from 2 µm to 7 µm. In some embodiments, the body section has a length of from 10 µm to 500 µm, such as from 20 µm to 490 µm, such as from 30 µm to 480 µm, such as from 40 µm to 470 µm, such as from 50 µm to 460 µm, such as from 60 µm to 450 µm, such as from 70 µm to 440 µm, such as from 80 µm to 430 µm, such as from 90 µm to 420 µm, such as from 100 µm to 410 µm, such as from 110 µm to 400 µm, such as from 120 µm to 390 µm, such as from 130 µm to 380 µm, such as from 140 µm to 370 µm and including from 150 µm to 360 µm. In some embodiments, the base section has a length of from 10 µm to 500 µm, such as from 20 µm to 490 µm, such as from 30 µm to 480 µm, such as from 40 µm to 470 µm, such as from 50 µm to 460 µm, such as from 60 µm to 450 µm, such as from 70 µm to 440 µm, such as from 80 µm to 430 µm, such as from 90 µm to 420 µm, such as from 100 µm to 410 µm, such as from 110 µm to 400 µm, such as from 120 µm to 390 µm, such as from 130 µm to 380 µm, such as from 140 µm to 370 µm and including from 150 µm to 360 µm. In some embodiments, the lattice microstructure of the polymeric microneedles is formed from lattice cells having a unit size of from 1 µm to 1000 µm, such as from 5 µm to 950 µm, such as from 10 µm to 900 µm, such as from 15 µm to 850 µm, such as from 20 µm to 800 µm, such as from 25 µm to 750 µm, such as from 30 µm to 700 µm, such as from 35 µm to 650 µm, such as from 40 µm to 600 µm, such as from 45 µm to 550 µm and including from 50 µm to 500 µm, for example from 200 µm to 500 µm. In embodiments, the polymeric microneedles has a volume of from 0.01 µL to 25 µL, such as from 0.02 µL to 24.5 µL, such as from 0.03 µL to 24 µL, such as from 0.04 µL to 23.5 µL, such as rom 0.05 µL to 23 µL, such as from 0.6 µL to 22.5 µL, such as from 0.07 µL to 22 µL, such as from 0.08 µL to 21.5 µL, such as from 0.09 µL to 21 µL, such as from 0.1 µL to 20 µL, such as from 0.5 µL to 19 µL, such as from 1 µL to 18 µL, such as from 2 µL to 17 µL, such as from 3 µL to 16 µL and including from 4 µL to 15 µL. Figure 1 depicts a polymeric structure having an array of polymeric microneedles of a microneedle array patch configured to puncture the skin of a subject according to certain embodiments. As shown in Figure 1, the array 100 of polymeric microneedles Attorney Docket No.: STAN-2203WO Stanford No.: S24-200 includes a substrate 101 and a plurality of microneedles 102 positioned on top of the substrate. The microneedles shown in Figure 1 have uniform height, but in certain instances the microneedles may have varying heights depending on the skin or tissue surface. Microneedles 102 include a tip portion 102a and a body portion 102b. In some instances, the polymeric microneedles have a beveled tip which makes a linear incision into the stratum corneum as compared to a cone-shaped tip which makes a point defect. In some instances, the microneedles are configured to penetrate through the epidermis into the ISF-rich dermis but not too deep to cause deep tissue damage. The polymeric microneedles of the polymeric structure have latticed tips which exhibit uniform penetration depth across the microneedle array patch as compared to microneedles having solid tips. As described above, the microneedle array patch includes a pressure plate configured for collecting a biological fluid sample from the puncture sites generated by insertion of the microneedle array. In some instances, the pressure plate is configured to wick biological fluid into the holes of the array such as through capillary action. In some embodiments, the pressure plate is configured to apply pressure around each of the puncture sites by the array of polymeric microneedles. In some instances, the applied pressure around each of the puncture sites creates a pressure gradient that drives biological fluid into the puncture sites. In some instances, the pressure plate is configured to maintain the puncture opening created by the microneedles. In some instances, the pressure plate is configured to facilitate fluid flow towards the center of the pressure plate. In some instances, the pressure plate is configured to ensure uniform pressure is applied across the plate by matching skin curvature. Depending on the size of each hole of the pressure plate, the holes of the pressure plate may be configured to collect 0.01 µL or more of the biological fluid, such as 0.05 µL or more, such as 0.1 µL or more, such as 0.2 µL or more, such as 0.3 µL or more, such as 0.4 µL, such as 0.5 µL or more, such as 1 µL or more, such as 2 µL or more, such as 3 µL or more, such as 4 µL or more, such as 5 µL and including 10 µL or more of the biological fluid. In some embodiments, each hole of the pressure plate has a volume of from 0.1 µL to 100 µL, such as from 0.5 µL to 90 µL, such as from 1 µL to 80 µL, such as from 5 µL to 70 µL and including a volume of from 2 µL to 25 µL. The pressure plate may be configured to collect biological fluid over a period of time of 1 Attorney Docket No.: STAN-2203WO Stanford No.: S24-200 second or more, such as 5 seconds or more, such as 10 seconds or more, such as 15 seconds or more, such as 30 seconds or more, such as 1 minute or more, such as 5 minutes or more, such as 10 minutes or more, such as 15 minutes or more, such as 30 minutes or more, such as 1 hour or more, such as 2 hours or more, such as 3 hours or more, such as 6 hours or more, such as 12 hours or more, such as 18 hours or more and including over a period of time of 24 hours or more. In certain instances, the pressure plate is configured to collect biological fluid sample at a rate of from 1 µL to 10 µL per minute, such as from 5 µL to 20 µL in 20 minutes. In some embodiments, the pressure plate includes a plurality of holes, such as 2 or more holes, such as 3 or more, such as 4 or more, such as 5 or more, such as 10 or more, such as 25 or more, such as 50 or more, such as 100 or more, such as 250 or more, such as 500 or more and including 1000 holes or more. In some instances, the pressure plate includes an array of holes. In some instances, the array of holes correspond to the array of polymeric microneedles of the polymeric structure. In some instances, the pressure plate is configured so that the array of polymeric microneedles are inserted through the holes of the pressure plate to puncture the skin surface of the subject. In some instances, the holes of the pressure plate are arranged in one or more lines. For example, the holes may be positioned along 2 or more parallel lines, such as 3 or more, such as 4 or more, such as 5 or more, such as 6 or more, such as 7 or more, such as 8 or more, such as 9 or more, such as 10 or more, such as 15 or more, such as 20 or more and including 25 or more parallel lines of holes. In certain instances, the holes are arranged into a geometric configuration, where arrangements of interest include, but are not limited to a square configuration, rectangular configuration, trapezoidal configuration, triangular configuration, hexagonal configuration, heptagonal configuration, octagonal configuration, nonagonal configuration, decagonal configuration, dodecagonal configuration, circular configuration, oval configuration as well as irregular shaped configurations. In certain instances, the holes are arranged in a random configuration. In some embodiments, the holes are separated from each other on the pressure plate by an average distance of from 1 µm to 1000 µm, such as from 2 µm to 950 µm, such as from 3 µm to 900 µm, such as from 4 µm to 850 µm, such as from 5 µm to 800 µm, such as from 6 µm to 750 µm, such as from 7 µm to 700 µm, such as from 8 µm to Attorney Docket No.: STAN-2203WO Stanford No.: S24-200 650 µm, such as from 9 µm to 600 µm, such as from 10 µm to 550 µm, such as from 15 µm to 500 µm, such as from 20 µm to 450 µm and including from 25 µm to 400 µm. The plurality of holes may each be the same size or pressure plates may include plurality of holes having different sizes. Each holes independently may have a depth of from 50 µm to 2000 µm, such as from 75 µm to 1950 µm, such as from 100 µm to 1900 µm, such as from 125 µm to 1850 µm, such as from 150 µm to 1800 µm, such as from 175 µm to 1750 µm, such as from 200 µm to 1700 µm, such as from 225 µm to 1650 µm, such as from 250 µm to 1600 µm, such as from 275 µm to 1550 µm and including from 300 µm to 1500 µm. Each holes independently may have a width (diameter when the polymeric microneedle has a circular cross-section) of from 50 µm to 1000 µm, such as from 75 µm to 950 µm, such as from 100 µm to 900 µm, such as from 125 µm to 850 µm, such as from 150 µm to 800 µm, such as from 175 µm to 750 µm, such as from 200 µm to 700 µm, such as from 225 µm to 650 µm, such as from 250 µm to 600 µm, such as from 275 µm to 550 µm and including from 300 µm to 500 µm. In some instances, the holes of the pressure plate have a circular cross-section. In some instances, the holes of the pressure plate have an oval cross-section. In some instances, the holes of the pressure plate have a polygonal cross-section, such as where the holes have a square cross-section, a triangular cross-section, a rectangular cross- section, a pentagonal cross-section or a hexagonal cross-section. In some embodiments, the geometry of the holes facilitate capillary action to collect the biological fluid through the holes. In some instances, the holes have a cross-sectional shape, depth and lateral dimension which is optimized for capillary action to collection the biological fluid. The size of the holes may have a width (or diameter when the holes are circular) of from 200 µm to 750 µm, such as from 300 µm to 675 µm. In some instances, the pressure plate has a height of from 300 µm to 2000 µm, such as from 500 µm to 1500 µm. In some instances, the depth of each hole is from 300 µm to 2000 µm, such as from 500 µm to 1500 µm. In some embodiments, each hole of the pressure plate has a volume of from 0.1 µL to 100 µL, such as from 0.5 µL to 90 µL, such as from 1 µL to 80 µL, such as from 5 µL to 70 µL and including a volume of from 2 µL to 25 µL. Figure 2 depicts pressure plates with holes having different lengths and cross- sections according to certain embodiments. The pressure plates shown have different heights which can depend on the length of the microneedles which are configured to be Attorney Docket No.: STAN-2203WO Stanford No.: S24-200 inserted therethrough. The length of the microneedles and the height of the pressure plate can provide for different volumes of interstitial fluid being collected. As shown in Figure 2, in some instances the holes in the pressure plates can be circular. In other instances, the holes in the pressure plates can be triangular or some other polygon. The sizes of the holes also vary depending on the width (or diameter) of the microneedles. In some instances, the geometry of the hole can facilitate capillary action to collect the biological fluid. In some embodiments, the holes of the pressure plate include a wall which extends from the surface of the pressure plate. In some instances, the wall is configured to be positioned within the puncture site generated by the inserted polymeric microneedle into the skin of the subject. In some instances, the wall is configured to keep the puncture site open and maintain flow for collecting the biological fluid. In some instances, the walls independently for each hole may have a depth of from 50 µm to 2000 µm, such as from 75 µm to 1950 µm, such as from 100 µm to 1900 µm, such as from 125 µm to 1850 µm, such as from 150 µm to 1800 µm, such as from 175 µm to 1750 µm, such as from 200 µm to 1700 µm, such as from 225 µm to 1650 µm, such as from 250 µm to 1600 µm, such as from 275 µm to 1550 µm and including from 300 µm to 1500 µm. Figure 3 depicts a pressure plate having walls which extends from the surface of the pressure plate according to certain embodiments. Pressure plate 300 includes a surface with holes 301 (here shown with circular cross-section) which pass through the pressure plate. The side of the pressure plate configured for contact with the skin surface of a subject includes walls 302 (in the shape of cylinders) which extend from each of the holes of the pressure plate. In some instances, the walls are inserted into the puncture site to maintain the puncture opening and facilitate collection of the biological sample such as through capillary action. In some embodiments, the pressure plate has a planar surface (e.g., flat surface). In some instances, the pressure plate has a concave surface. In some instances, the pressure plate has a convex surface. In certain instances, the pressure plate has a surface that matches the skin curvature of the subject. In certain instances, the pressure plate has a shape-conforming surface. In certain instances, the pressure Attorney Docket No.: STAN-2203WO Stanford No.: S24-200 plate has a shape-memory surface where the pressure plate conforms to the shape of the surface and retains this shape. Figure 4 depicts pressure plates having an array of holes configured for collecting a biological fluid sample from each skin puncture site by the array of polymeric microneedles according to certain embodiments. The pressure plates can be flat having a planar surface or can have curved surfaces such as concave and convex surfaces. In certain instances, the pressure plate has a shape that conforms to the surface of the skin, such as through shape-memory. As shown in Figure 4, pressure plate 400 has a convex top surface which can create an additional gradient as higher pressure towards edges of the pressure plate coaxes interstitial fluid towards the middle of the microneedle array patch. Pressure plate 401 has a concave top surface and has a skin curvature-matched surface structure. In some instances, the curvature-matched surface ensures equal pressure distribution across all penetration sites. In some embodiments, the pressure plate includes a reservoir for collecting the biological fluid through the holes. In some instances, the pressure plate includes a plurality of reservoirs, such as 2 or more, such as 3 or more, such as 4 or more, such as 5 or more, such as 6 or more, such as 7 or more, such as 8 or more, such as 9 or more, such as 10 or more, such as 15 or more, such as 25 or more, such as 50 or more, such as 100 or more and including 250 or more reservoirs. In some instances, each hole of the pressure plate is in fluid communication with its own reservoir. In other instances, two or more of the holes of the pressure plate share a reservoir where the two or more holes are in fluid communication with a reservoir, such as where 3 or more are in fluid communication with the reservoir, such as 4 or more, such as 5 or more, such as 6 or more, such as 7 or more, such as 8 or more, such as 9 or more and including 10 or more. In other instances, the pressure plate includes a single reservoir which collects the biological fluid which is drawn through all of the holes of the pressure plate. Each reservoir can have a volume that varies depending on the number of holes in fluid communication with the reservoir, such as a volume of from 0.001 mL to 1000 mL, such as from 0.005 mL to 900 mL, such as from 0.01 mL to 800 mL, such as from 0.05 mL to 700 mL, such as from 0.1 mL to 600 mL, such as from 0.5 mL to 500 mL, such as from 1 mL to 400 mL, such as from 5 mL to 300 mL, such as from 10 mL to 200 mL and including from 15 mL to 150 mL. Attorney Docket No.: STAN-2203WO Stanford No.: S24-200 In some embodiments, the polymeric structure having the array of polymeric microneedles is integrated together with the pressure plate. In some instances, the microneedle array patch has a plurality of polymeric microneedles which extend from the surface of a substrate (pressure plate) and the substrate has holes which pass through the substrate and through each of the microneedles. In some instances, the integrated array of polymeric microneedles with the pressure plate form a single polymeric structure. In some instances, the pressure plate of the integrated system includes a reservoir for collecting the biological fluid. In some instances, the reservoir has a hydrophilic surface. In some instances, the reservoir has a surface that is configured to facilitate wicking of the biological fluid into the reservoir, such as by capillary action. Figure 5 depicts an integrated one-part microneedle array system according to certain embodiments. As shown in Figure 5, the microneedle array patch includes a substrate pressure plate which has a plurality of holes that pass through the substrate and through a plurality of microneedles that are formed on the surface of the pressure plate. Each hole corresponds to a single microneedle of the plurality of polymeric microneedles. The integrated microneedle array patch shown in Figure 5 has a reservoir on the opposite side of the pressure plate from the microneedles. The reservoir is configured to collect and store a biological fluid. The interior surface of the reservoir has a hydrophilic surface in order to facilitate wicking and capillary action to draw the biological fluid into the reservoir through the microneedles. The inset of Figure 5 shows that the latticed microneedles can also have a hydrophilic interior to further facilitate wicking of the biological fluid into the reservoir. In certain embodiments, the pressure plate includes a pressure sensitive adhesive, such as for maintaining the pressure plate in contact with the skin surface of a subject for an extended period of time. Pressure sensitive adhesives may include, but are not limited to, poly-isobutene adhesives, poly-isobutylene adhesives, poly- isobutene / polyisobutylene adhesive mixtures, carboxylated polymers, acrylic or acrylate copolymers, such as carboxylated acrylate copolymers. Where the pressure sensitive adhesive includes polybutene, the polybutene may be saturated polybutene. Alternatively, the polybutene may be unsaturated polybutene. Still further, the polybutene may be a mixture or combination of saturated polybutene and unsaturated polybutene. In some embodiments, the pressure sensitive adhesive Attorney Docket No.: STAN-2203WO Stanford No.: S24-200 may include a composition that is, or is substantially the same as, the composition of Indopol® L-2, Indopol® L-3, Indopol® L-6, Indopol® L-8, Indopol® L-14, Indopol® H-7, Indopol® H-8, Indopol® H-15, Indopol® H-25, Indopol® H-35, Indopol® H-50, Indopol® H-100, Indopol® H-300, Indopol® H-1200, Indopol® H-1500, Indopol® H-1900, Indopol® H-2100, Indopol® H-6000, Indopol® H-18000, Panalane® L-14E, Panalane® H-300E and combinations thereof. In certain embodiments, the polybutene pressure-sensitive adhesive is Indopol® H-1900. In other embodiments, the polybutene pressure-sensitive adhesive is Panalane® H-300E. Acrylate copolymers of interest include copolymers of various monomers, such as “soft” monomers, “hard” monomers or “functional” monomers. The acrylate copolymers can be composed of a copolymer including bipolymer (i.e., made with two monomers), a terpolymer (i.e., made with three monomers), or a tetrapolymer (i.e., made with four monomers), or copolymers having greater numbers of monomers. The acrylate copolymers may be crosslinked or non-crosslinked. The polymers can be cross-linked by known methods to provide the desired polymers. The monomers from of the acrylate copolymers may include at least two or more exemplary components selected from the group including acrylic acids, alkyl acrylates, methacrylates, copolymerizable secondary monomers or monomers with functional groups. Monomers (“soft” and “hard” monomers) may be methoxyethyl acrylate, ethyl acrylate, butyl acrylate, butyl methacrylate, hexyl acrylate, hexyl methacrylate, 2-ethylbutyl acrylate, 2-ethylbutyl methacrylate, isooctyl acrylate, isooctyl methacrylate, 2-ethylhexyl acrylate, 2-ethylhexyl methacrylate, decyl acrylate, decyl methacrylate, dodecyl acrylate, dodecyl methacrylate, tridecyl acrylate, tridecyl methacrylate, acrylonitrile, methoxyethyl acrylate, methoxyethyl methacrylate, and the like. Additional examples of acrylic adhesive monomers are described in Satas, "Acrylic Adhesives," Handbook of Pressure-Sensitive Adhesive Technology, 2nd ed., pp.396-456 (D. Satas, ed.), Van Nostrand Reinhold, New York (1989), the disclosure of which is herein incorporated by reference. In some embodiments, the pressure sensitive adhesive is an acrylate-vinyl acetate copolymer. In some embodiments, the pressure sensitive adhesive may include a composition that is, or is substantially the same as, the composition of Duro-Tak® 87-9301, Duro-Tak® 87- 200A, Duro-Tak®87-2353, Duro-Tak®87-2100, Duro-Tak®87-2051, Duro-Tak®87-2052, Duro-Tak®87-2194, Duro-Tak®87-2677, Duro-Tak®87-201A, Duro-Tak®87-2979, Duro- Attorney Docket No.: STAN-2203WO Stanford No.: S24-200 Tak®87-2510, Duro-Tak®87-2516, Duro-Tak®87-387, Duro-Tak®87-4287, Duro- Tak®87-2287,and Duro-Tak®87-2074 and combinations thereof. The term “substantially the same” as used herein refers to a composition that is an acrylate-vinyl acetate copolymer in an organic solvent solution. In certain embodiments, the acrylic pressure-sensitive adhesive is Duro-Tak® 87-2054. METHODS FORCOLLECTING ABIOLOGICALFLUIDSAMPLE WITH AMICRONEEDLEARRAYPATCH Aspects of the present disclosure also include methods for collecting a biological fluid sample from a subject with a microneedle array patch. The biological fluid sample may be collected into the holes of the pressure plate by any convenient protocol, such as for example by capillary action. In embodiments, the biological fluid sample is collected from one or more of the subcutis, dermis and epidermis, including the stratum corneum, stratum germinativum, stratum spinosum and stratum basale of the subject. In certain instances, the biological fluid sample is interstitial fluid. In certain instances, the biological fluid sample is dermal fluid. In certain instances, the biological fluid sample is blood. In some embodiments, methods include collecting a biological fluid sample from the subject (e.g., interstitial fluid, dermal fluid) for detecting an analyte present in the biological sample, such as for detecting glucose. In some instances, pressure is applied to the pressure plate at the surface of the skin to collect sample into the holes of the pressure plate. Accordingly, the microneedle array patch may be applied at any convenient location, such as for example, the arms, legs, buttocks, abdomen, back, neck, scrotum, vagina, face, behind the ear, buccally as well as sublingually. In describing methods of the present invention, the term “subject” is meant the person or organism to which the patch is applied and maintained in contact. As such, subjects of the invention may include but are not limited to mammals, e.g., humans and other primates, such as chimpanzees and other apes and monkey species; and the like, where in certain embodiments the subject are humans. The term subject is also meant to include a person or organism of any age, weight or other physical characteristic, where the subjects may be an adult, a child, an infant or a newborn. Attorney Docket No.: STAN-2203WO Stanford No.: S24-200 In some embodiments, methods include extended collection of the biological fluid sample from the skin of the subject. By “extended collection” is meant that the microneedle array patch are configured to provide for collection of the biological fluid sample compound over an extended period of time, such as over the course of minutes and hours including 1 minute or longer, such as 2 minutes or longer, such as 4 minutes or longer, such as 8 minutes or longer, such as 12 minutes or longer, such as 24 minutes or longer, such as 48 minutes or longer, such as 72 minutes or longer, such as 96 minutes or longer, such as 120 minutes or longer, such as 144 minutes or longer and including 168 minutes or longer. In certain embodiments, protocols may include multiple collection intervals. By “multiple collection intervals” is meant more than one microneedle array patch is applied and maintained in contact with the subject in a sequential manner. As such, a microneedle array patch is removed from contact with the subject and a new patch is reapplied to the subject. In practicing methods of the invention, collection regimens may include two or more collection intervals, such as three or more collection intervals, such as four or more collection intervals, such as five or more collection intervals, including ten or more collection intervals. The duration between collection intervals in a multiple collection interval protocol may vary. For example, the duration between dosage intervals in a multiple dosage treatment protocol may be predetermined and follow at regular intervals. As such, the time between collection intervals may vary and may be 1 day or longer, such as 2 days or longer, such as 3 days or longer, such as 4 days or longer, such as 5 days or longer, such as 6 days or longer, such as 7 days or longer, such as 10 days or longer, including 30 days or longer. An upper limit period of time between collection intervals is, in some instances, 30 days or shorter, such as 28 days or shorter, such as 21 days or shorter, such as 14 days or shorter, such as 7 days or shorter and including 3 days or shorter. In certain embodiments, the time between dosage intervals ranges such as from 2 days to 30 days, such as from 3 days to 28 days, such as from 4 days to 21 days, such as from 5 days to 14 days and including from 6 days to 10 days. The location on the subject for collecting biological fluid sample in multiple collection regimens may be the same or different from the location on the subject where the previous microneedle array patch was removed. For example, if a first microneedle Attorney Docket No.: STAN-2203WO Stanford No.: S24-200 array patch is applied and maintained on the leg of the subject, one or more subsequent microneedle array patches may be reapplied to the same position on the leg of the subject. On the other hand, if a first microneedle array patch was applied and maintained on the leg of the subject, one or more subsequent microneedle array patches may be reapplied to a different position, such as the abdomen or back of the subject. In some instances, the method includes positioning the pressure plate on the surface of the skin of the subject and puncturing the skin surface by inserting the array of polymeric microneedles through the array of holes of the pressure plate. In some instances, the method includes retracting the array of microneedles from the skin surface. In some instances, the array of microneedles is inserted into the skin surface and retracted immediately after puncturing the skin surface. In other instances, the array of microneedles is inserted into the skin surface and maintained in the skin of the subject for 30 seconds or more, such as 1 minute or more and including for 10 minutes or more. In some instances, the array of microneedles is inserted into the skin surface and maintained in the skin of the subject for a period of time of from 1 minute to 30 minutes. In certain instances, the pressure plate applied to the skin surface of the subject to collect biological fluid sample into the holes of the array and maintained in contact with the subject for an extended period of time, such as for 1 minute or more, such as 5 minutes or more and including for 10 minutes or more. In some instances, the pressure plate is maintained in contact with the skin (e.g., by applying pressure to the skin of the subject with the pressure plate) for 30 minutes or longer. In certain embodiments, the array of microneedles is inserted into the skin surface and maintained in the skin of the subject for 10 minutes or less, such as for 9 minutes or less, such as for 8 minutes or less, such as for 7 minutes or less, such as for 6 minutes or less, such as for 5 minutes or less, such as for 4 minutes or less, such as for 3 minutes or less, such as for 2 minutes or less and including for 1 minute or less. In certain instances, the pressure plate applied to the skin surface of the subject and removed within 15 minutes or less, such as within 5 minutes or less and including within 1 minute or less. In some instances, the biological fluid sample is collected at a rate of from 1 µL to 50 µL per minute, such as from 1 µL to 45 µL per minute, such as from 1 µL to 40 µL per minute, such as from 1 µL to 35 µL per minute, such as from 1 µL to 30 µL per minute, such as from 1 µL to 25 µL per minute, such as from 1 µL to 20 µL per minute, such as Attorney Docket No.: STAN-2203WO Stanford No.: S24-200 from 1 µL to 15 µL per minute, such as from 1 µL to 10 µL per minute. In some instances, the biological fluid sample is collected at a rate of from 1 µL to 50 µL in 20 minutes, such as from 1 µL to 45 µL in 20 minutes, such as from 1 µL to 40 µL in 20 minutes, such as from 1 µL to 35 µL in 20 minutes, such as from 1 µL to 30 µL in 20 minutes, such as from 1 µL to 25 µL in 20 minutes, such as from 1 µL to 20 µL in 20 minutes, such as from 1 µL to 15 µL in 20 minutes, such as from 1 µL to 10 µL in 20 minutes, such as from 5 µL to 20 µL in 20 minutes. In certain instances, the biological fluid sample is collected at a rate of from 1 µL to 50 µL in 5 minutes, such as from 1 µL to 45 µL in 5 minutes, such as from 1 µL to 40 µL in 5 minutes, such as from 1 µL to 35 µL in 5 minutes, such as from 1 µL to 30 µL in 5 minutes, such as from 1 µL to 25 µL in 5 minutes, such as from 1 µL to 20 µL in 5 minutes, such as from 1 µL to 15 µL in 5 minutes, such as from 1 µL to 10 µL in 5 minutes, such as from 5 µL to 20 µL in 5 minutes, including collecting 10 µL in 5 minutes. Figure 6 depicts collecting a biological fluid (e.g., interstitial fluid) with a microneedle array patch according to certain embodiments. At step 1, the microneedles of a polymeric structure having a plurality of microneedles are inserted through the holes of a pressure plate to puncture the skin. Here, the microneedles are removed immediately after puncturing the skin. Pressure is applied to the pressure plate at step 2 to express the interstitial fluid from the puncture sites. The pressure can be applied manually (e.g., with the thumb) or can be applied with a block for a predetermined period of time (e.g., for 5 minutes). Pressure applied to the pressure plate facilitates the expression of the interstitial fluid into the holes and when present, into the reservoir on the pressure plate. In certain embodiments, methods further include the step of removing the microneedle array patch from contact with the subject at the conclusion of a collection interval. For example, the microneedle array patch may be removed from contact with the subject after maintaining the patch in contact with the subject for 0.5 hours or more, such as 1 hour or more, such as 2 hours or more, such as 4 hours or more, such as 8 hours or more, such as 12 hours or more, such as 24 hours or more, such as 36 hours or more, such as 48 hours or more, such as 60 hours or more, such as 72 hours or more, such as 96 hours or more, such as 120 hours or more, including 144 hours or more, and including 168 hours or more. An upper limit for the amount of time the Attorney Docket No.: STAN-2203WO Stanford No.: S24-200 polymeric structure is maintained in contact with a subject before removal is, in some instances, 168 hours or shorter, such as 144 hours or shorter, such as 120 hours or shorter, such as 96 hours or shorter, such as 72 hours or shorter, such as 48 hours or shorter, such as 24 hours or shorter, such as 12 hours or shorter, such as 8 hours or shorter, such as 4 hours or shorter and including 2 hours or shorter. The microneedle array patch having a plurality of polymeric microneedles according to embodiments of the invention are non-irritable to the skin of the subject at the site of application. Irritation of the skin is referred to herein in its general sense to refer to adverse effects, discoloration or damage to the skin, such as for example, redness, pain, swelling or dryness. As such, in practicing methods with the subject polymeric structures the quality of the skin remains normal and is consistent throughout the entire dosage or collection interval. In some embodiments, skin irritation is evaluated to determine the quality and color of the skin at the application site and to determine whether any damage, pain, swelling or dryness has resulted from maintaining the polymeric structure in contact with the subject. The skin may be evaluated for irritation by any convenient protocol, such as for example using the Draize scale, as disclosed in Draize, J. H., Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, pp.46-49, The Association of Food and Drug Officials of the United States: Austin, Texas, the disclosure of which is herein incorporated by reference. In particular, the skin may be evaluated at the patch application site for erythema or edema. For example, grades for erythema and edema may be assigned based on visual observation or palpation: Erythema: 0=no visible redness; 1=very slight redness (just perceptible); 2=slight but defined redness; 3=moderately intense redness; 4=severe erythema (dark red discoloration of the skin) 5 = eschar formation Edema: 0=no visible reactions or swelling; 1=very mild edema (just perceptible swelling); 2=mild edema (corners of area are well defined due to swelling); 3=moderate edema (up to 1 mm swelling); 4=severe edema (more than 1 mm swelling). The site of application may be evaluated for skin irritation at any time during the subject methods. In some instances, the skin is evaluated for irritation while maintaining Attorney Docket No.: STAN-2203WO Stanford No.: S24-200 the polymeric structure in contact with the subject by observing or palpating the skin at regular intervals, e.g., every 0.25 hours, every 0.5 hours, every 1 hour, every 2 hours, every 4 hours, every 12 hours, every 24 hours, including every 72 hours, or some other interval. For instance, the site of application may be evaluated for skin irritation while maintaining the polymeric structure in contact with the subject, such as 15 minutes after applying the polymeric structure to the subject, 30 minutes after applying the polymeric structure, 1 hour after applying the transdermal delivery device, 2 hours after applying the patch, 4 hours after applying the polymeric structure, 8 hours after applying the polymeric structure, 12 hours after applying the polymeric structure, 24 hours after applying the polymeric structure, 48 hours after applying the polymeric structure, 72 hours after applying the polymeric structure, 76 hours after applying the polymeric structure, 80 hours after applying the polymeric structure, 84 hours after applying the polymeric structure, 96 hours after applying the polymeric structure, 120 hours after applying the polymeric structure, including 168 hours after applying the polymeric structure. METHODS FOR MAKING A MICRONEEDLE ARRAY PATCH HAVING A POLYMERIC STRUCTURE WITH AN ARRAY OF MICRONEEDLES AND A PRESSURE PLATE Aspects of the disclosure also include methods for making a microneedle array patch having a polymeric structure having one or more polymeric microneedles and a pressure plate as described herein. Methods according to certain embodiments is a high resolution continuous additive processing method that includes irradiating a polymerizable composition positioned between a build elevator and a build surface to generate a polymerizable composition having a first polymerized region of the polymerizable composition in contact with the build elevator and a first non-polymerized region of the polymerizable composition in contact with the build surface; displacing the build elevator away from the build surface; irradiating the first non-polymerized region of the polymerizable composition to generate a second polymerized region of the polymerizable composition in contact with the first polymerized region and a second non- polymerized region in contact with the build surface and repeating in a manner sufficient to generate the polymeric structure. These steps are repeated in a manner sufficient to generate a polymeric structure which exhibits a macrostructural change in response to Attorney Docket No.: STAN-2203WO Stanford No.: S24-200 an applied stimulus. For example, the steps may be repeated 2 or more times, such as 3 or more times, such as 4 or more times, such as 5 or more times, such as 10 or more times, such as 20 or more times, such as 30 or more times, such as 40 or more times, such as 50 or more times, such as 100 or more times, such as 250 or more times, such as 500 or more times and including 1000 or more times. In some embodiments, the polymerizable composition is irradiated with a light beam generator component of a micro-digital light projection system. In some instances, the light source is a broadband light source that emits light having wavelengths from 400 nm to 1000 nm. In some instances, the broadband light source is a halogen lamp, deuterium arc lamp, xenon arc lamp, stabilized fiber-coupled broadband light source, a broadband LED with continuous spectrum, superluminescent emitting diode, semiconductor light emitting diode, wide spectrum LED white light source, a multi-LED integrated white light source, among other broadband light sources or any combination thereof. In some instances, the light source is a narrow band light source emitting a particular wavelength or a narrow range of wavelengths. In some instances, the narrow band light sources emit light having a narrow range of wavelengths, such as for example, 50 nm or less, such as 40 nm or less, such as 30 nm or less, such as 25 nm or less, such as 20 nm or less, such as 15 nm or less, such as 10 nm or less, such as 5 nm or less, such as 2 nm or less and including light sources which emit a specific wavelength of light. In some instances, the polymerizable composition is irradiated with a narrow band light source such as a narrow wavelength LED, laser diode or a broadband light source coupled to one or more optical bandpass filters, diffraction gratings, monochromators or any combination thereof. In certain embodiments, the light source is a stroboscopic light source and the polymerizable composition is illuminated with periodic flashes of light, such as where the polymerizable composition is irradiated at a frequency of 0.01 kHz or greater, such as 0.05 kHz or greater, such as 0.1 kHz or greater, such as 0.5 kHz or greater, such as 1 kHz or greater, such as 2.5 kHz or greater, such as 5 kHz or greater, such as 10 kHz or greater, such as 25 kHz or greater, such as 50 kHz or greater and including 100 kHz or greater. In certain instances, the polymerizable composition is irradiated with a laser, such as pulsed laser or a continuous wave laser. Attorney Docket No.: STAN-2203WO Stanford No.: S24-200 In some embodiments, the polymerizable composition is in contact with the build elevator and the build surface. In some instances, methods include irradiating the polymerizable composition for 1 second or longer to bond the first polymerized region of the polymerizable composition to the build elevator, such as from 5 seconds longer, such as for 10 seconds or longer, such as for 20 seconds or longer, such as for 30 seconds or longer, such as for 1 minute or longer, such as for 5 minutes or longer and including for 10 minutes or longer. In some embodiments, the build elevator is displaced away from the build surface after the first polymerized region of the polymerizable composition is bonded to the build elevator. In some instances, the build elevator is displaced in increments of 0.001 µm or more, such as 0.005 µm or more, such as 0.01 µm or more, such as 0.05 µm or more, such as 0.1 µm or more, such as 0.5 µm or more, such as 1 µm or more, such as 2 µm or more, such as 3 µm or more, such as 4 µm or more, such as 5 µm or more and including in increments of 10 µm or more. In certain instances, the build elevator is displaced in increments of from 0.001 µm to 20 µm, such as from 0.005 µm to 19 µm, such as from 0.01 µm to 18 µm, such as from 0.05 µm to 17 µm, such as from 0.1 µm to 16 µm, such as from 0.2 µm to 17 µm, such as from 0.3 µm to 16 µm, such as from 0.4 µm to 15 µm, such as from 0.5 µm to 14 µm, such as from 0.6 µm to 13 µm, such as from 0.7 µm to 12 µm, such as from 0.8 µm to 11 µm and including from 0.9 µm to 10 µm. In certain instances, polymerizable composition is added to the build surface after each displacement of the build elevator away from the build surface. In some instances, the polymerizable composition is continuously added to the build surface. In other instances, the polymerizable composition is added to the build surface in discreet intervals each having a predetermined amount. In some embodiments, the polymerizable composition is selected from polycaprolactone, polyglycolic acid, polylactic acid, polylactic-co-glycolic acid, polyethylene glycol, thiol-enes, anhydrides, polyacrylic acid, poly methylmethacrylate, polyvinyl alcohol, polyvinylpyrrolidone, vinyl carbonates, vinyl esters, acrylamides, hyaluronic acid, chitosan, collagen, gelatin, carboxymethylcellulose, and blends or copolymers thereof. In certain embodiments, polymeric microneedles are formed from polyethylene glycol dimethacrylate (PEGDMA). Attorney Docket No.: STAN-2203WO Stanford No.: S24-200 In some embodiments, the polymerizable composition is irradiated through build surface. In some instances, the polymerizable composition is irradiated in the presence of a polymerization inhibitor. In certain embodiments, the polymerizable composition is continuously polymerized while displacing the build elevator away from the build surface. In certain cases, the polymerization inhibitor is oxygen and the build surface is permeable to oxygen. In certain instances, polymerizing the polymerizable composition in the presence of a polymerization inhibitor such as oxygen enables continuous (i.e., not layer-by-layer) generation the lattice microstructure with a liquid “dead zone” at the interface between the build surface and the building polymeric microneedle. In some instances, the dead zone is generated because oxygen acts as a polymerization inhibitor, passing through the oxygen-permeable build surface. Photopolymerization cannot occur in the oxygen containing “dead zone” region such that this region remains fluid, and the polymerized component in contact with the build surface so that the building lattice microstructure does not physically attach to the build surface. In some embodiments, the polymeric structures described (e.g., one or more of the polymeric structure having the array of polymeric microneedles and the pressure plate having an array of holes) are polymerized using high resolution continuous liquid interface production such as described in International Patent Publication No. WO 2023 / 049267, the disclosure of which is herein incorporated by reference. In certain embodiments, the polymerizable composition is polymerized using a liquid interface polymerization module that is a continuous liquid interface production (CLIP) system such as that described in International Patent Publication No. WO 2014 / 126837; U.S. Patent Publication Nos.2018 / 0064920; 2017 / 0095972; 2021 / 0246252 and U.S. Patent Publication Nos.10,155,882; 10,792,857, the disclosures of which are herein incorporated by reference. In certain embodiments, the polymeric structure is generated by injection continuous liquid interface production by conveying the polymerizable composition through a conduit into a space between a build elevator and a build surface of a liquid interface production module, such as described in International Patent Application No. PCT / US2023 / 15406 filed on March 16, 2023, the disclosure of which is herein incorporated by reference. In some embodiments, methods include irradiating the polymerizable composition with a micro-digital light projection system as described in detail above. In Attorney Docket No.: STAN-2203WO Stanford No.: S24-200 some instances, methods include determining a focal plane on the build surface using the micro-digital light projection system. In some embodiments, determining the focal plane on the build surface includes irradiating the build surface with a stroboscopic light source through the tube lens and displacing the build surface until the light is focused on the build surface through the tube lens. In certain embodiments, methods for determining the focal plane on the build surface includes irradiating build surface with the stroboscopic light source with periodic flashes of light. For example, the frequency of each light pulse may be 0.0001 kHz or greater, such as 0.0005 kHz or greater, such as 0.001 kHz or greater, such as 0.005 kHz or greater, such as 0.01 kHz or greater, such as 0.05 kHz or greater, such as 0.1 kHz or greater, such as 0.5 kHz or greater, such as 1 kHz or greater, such as 2.5 kHz or greater, such as 5 kHz or greater, such as 10 kHz or greater, such as 25 kHz or greater, such as 50 kHz or greater and including 100 kHz or greater. In certain instances, the frequency of pulsed irradiation by the light source ranges from 0.00001 kHz to 1000 kHz, such as from 0.00005 kHz to 900 kHz, such as from 0.0001 kHz to 800 kHz, such as from 0.0005 kHz to 700 kHz, such as from 0.001 kHz to 600 kHz, such as from 0.005 kHz to 500 kHz, such as from 0.01 kHz to 400 kHz, such as from 0.05 kHz to 300 kHz, such as from 0.1 kHz to 200 kHz and including from 1 kHz to 100 kHz. The duration of light irradiation for each light pulse (i.e., pulse width) may vary and may be 0.000001 ms or more, such as 0.000005 ms or more, such as 0.00001 ms or more, such as 0.00005 ms or more, such as 0.0001 ms or more, such as 0.0005 ms or more, such as 0.001 ms or more, such as 0.005 ms or more, such as 0.01 ms or more, such as 0.05 ms or more, such as 0.1 ms or more, such as 0.5 ms or more, such as 1 ms or more, such as 2 ms or more, such as 3 ms or more, such as 4 ms or more, such as 5 ms or more, such as 10 ms or more, such as 25 ms or more, such as 50 ms or more, such as 100 ms or more and including 500 ms or more. For example, the duration of light irradiation may range from 0.000001 ms to 1000 ms, such as from 0.000005 ms to 950 ms, such as from 0.00001 ms to 900 ms, such as from 0.00005 ms to 850 ms, such as from 0.0001 ms to 800 ms, such as from 0.0005 ms to 750 ms, such as from 0.001 ms to 700 ms, such as from 0.005 ms to 650 ms, such as from 0.01 ms to 600 ms, such as from 0.05 ms to 550 ms, such as from 0.1 ms to 500 ms, such as from 0.5 ms to 450 ms, such as from 1 ms to 400 ms, such as from 5 ms to 350 ms and including from 10 ms to 300 ms. In some instances, methods include irradiating the build Attorney Docket No.: STAN-2203WO Stanford No.: S24-200 surface with a plane of light having a projected image pattern with the stroboscopic light source. In some instances, determining the focal plane on the build surface includes adjusting the focus of the tube lens. In some instances, the focal point of the tube lens is increased to adjust the focus onto the build surface. For example, the focal point may be increased by 1 µm or more, such as by 5 µm or more, such as by 10 µm or more, such as by 50 µm or more, such as by 100 µm or more, such as by 500 µm or more, such as by 1 mm or more, such as by 5 mm or more, such as by 10 mm or more, such as by 50 mm or more and including by 100 mm or more. In some instances, the focal point of the tube lens is decreased to adjust the focus onto the build surface. For example, the focal point may be decreased by 1 µm or more, such as by 5 µm or more, such as by 10 µm or more, such as by 50 µm or more, such as by 100 µm or more, such as by 500 µm or more, such as by 1 mm or more, such as by 5 mm or more, such as by 10 mm or more, such as by 50 mm or more and including by 100 mm or more. In some embodiments, methods include displacing the build surface until the projected image pattern is in focus with the build surface. The build surface and build elevator may be displaced using any convenient displacement protocol, such as manually (i.e., movement of the build surface or build elevator directly by hand), with assistance by a mechanical device or by a motor actuated displacement device. For example, in some embodiments the build surface or build elevator is moved with a mechanically actuated translation stage, mechanical leadscrew assembly, mechanical slide device, mechanical lateral motion device, mechanically operated geared translation device. In other embodiments, the build surface or build elevator is moved with a motor actuated translation stage, leadscrew translation assembly, geared translation device, such as those employing a stepper motor, servo motor, brushless electric motor, brushed DC motor, micro-step drive motor, high resolution stepper motor, among other types of motors. In some instances, the build surface is displaced by 1 µm or more, such as by 5 µm or more, such as by 10 µm or more, such as by 50 µm or more, such as by 100 µm or more and including by 500 µm or more. In certain embodiments, the build surface is displaced by 400 µm or less, such as 350 µm or less, such as by 300 µm or less, such as by 250 µm or less, such as by 200 µm or less, such as by 150 µm or less, such as by 100 µm or less and including by 50 µm or less. Attorney Docket No.: STAN-2203WO Stanford No.: S24-200 In some instances, methods include generating an image stack having a plurality of the projected image patterns. The image stack may include 2 or more projected image patterns, such as 3 or more, such as 4 or more, such as 5 or more, such as 10 or more and including 25 or more projected image patterns. In certain instances, methods include determining the focal plane of the build surface based on the generated image stack. In embodiments, methods as described here for generating polymeric microstructures (e.g., polymeric microneedles) having a lattice microstructure provide for a resolution of 10 µm or less, such as 5 µm or less. In certain embodiments, the subject methods provide for a resolution of from 1.0 µm to 4 µm, such as from 1.5 µm to 3.8 µm. KITS Kits for use in practicing certain methods described herein are also provided. In certain embodiments, the kits include one or more components of the microneedle array patches as described above. In some instances, kits include at least one polymeric structure having an array of polymeric microneedles configured to puncture the skin of a subject and at least one pressure plate comprising an array of holes configured for collecting a biological fluid sample from each skin puncture site by the array of polymeric microneedles. In some embodiments, kits include an adhesive overlay, such as a backing layer having a pressure sensitive adhesive. In a given kit that includes two or more of the subject polymeric structures having an array of microneedles or two or more pressure plates, each component may be individually packaged or present within a common container. In certain embodiments, the kits will further include instructions for practicing the subject methods or means for obtaining the same (e.g., a website URL directing the user to a webpage which provides the instructions), where these instructions may be printed on a substrate, where substrate may be one or more of: a package insert, the packaging, reagent containers and the like. Yet another form of these instructions is a computer readable medium, e.g., diskette, compact disk (CD), portable flash drive, USB storage, DVD, Blu-ray disk, etc.), and the like, on which the information has been recorded. Yet another form of these instructions that may be present is a website address which may be used via the internet to access the information at a removed site. Attorney Docket No.: STAN-2203WO Stanford No.: S24-200 EXAMPLES The following examples are put forth so as to provide those of ordinary skill in the art with a complete disclosure and description of how to make and use the present invention, and are not intended to limit the scope of what the inventors regard as their invention. Introduction Interstitial fluid (ISF) from the skin is a promising diagnostic specimen because 1) it has significant overlap in metabolomic, transcriptomic, and proteomic content with plasma, making it a viable alternative to phlebotomy; 2) there are novel biomarkers in ISF such as exosome enrichment that may enable new fundamental research and diagnostic tests; and 3) its collection can be performed with minimal pain by the patient on themselves or by untrained personnel. The inventors have found that dermal ISF research has been hindered by the lack of a reliable, minimally invasive collection method that can consistently retrieve useful volumes of ISF quickly. A desirable practical target is to collect 10 µL of ISF in minutes. Historically, ISF has been collected using invasive methods such as wicking, suction blister formation, or microdialysis, which often require local anesthesia and can take days to weeks for the skin to fully recover from. The use of microneedles is a less invasive method for sampling ISF, with the benefit of minimal pain and tissue injury that usually resolves within 24 hours. However, compared to the more invasive methods, microneedles generally collect 10-100 times less volume. In addition, it takes more time for conventional microneedles to extract a biological sample. For example, conventional microneedles average 2-5 µL of sample collection in 20 minutes or more than 1 hour if more than 10 µL is desired. Additionally, usability limitations remain, such as the need for a desktop vacuum pump, or glass capillary tubes that are worn during collection. These drawbacks continue to limit the adoption of current conventional ISF sampling devices. The microneedle patch arrays described herein are novel one- or two-part systems that include a polymeric structure having an array of microneedles and a plate with an array of holes that matches the polymeric microneedle structure. (see e.g., the microneedle array patch systems shown in Figures 5 and 6). To collect ISF, the plate is Attorney Docket No.: STAN-2203WO Stanford No.: S24-200 placed on the skin site, and microneedles are inserted through the holes to puncture the skin. The MAP is then removed, followed by pressure application to the plate to express ISF from the puncture sites. As ISF is expressed, the fluid is collected in the holes by capillary force. In some embodiments, the flow of ISF in the dermal matrix is governed by Darcy’s law Q = K∇P, where Q is flow / area, K is conductance, and P is pressure. To maximize ISF collection, the collection area and ∇P in three-dimensional space need to be maximized. By removing the MAP, the entire puncture site surface area receives ISF flow, and positive pressure from tissue distension at the puncture site is avoided. By using a plate with holes to apply pressure, the pressure gradient is maximized both across the depth and the lateral dimensions of the skin. In some embodiments, the device collects 5-20 µL in 5 minutes, which is 5-10 times faster than existing devices. Furthermore, the design is self-contained and requires no external implements to use. Examples of Polymeric Structure having Plurality of Microneedle Designs The ISF collection performance can be optimized based on the MAP design. Microneedle height and tip angle influence the skin penetration depth. A design that penetrates through the epidermis into the ISF-rich dermis, but not so deep as to cause excessive tissue damage, is desirable. The geometry of the microneedles also affects the uniformity of penetration across a patch. A latticed design (Figure 1) for the tip tends to penetrate more uniformly than a solid design. Finally, the shape and size of the skin tear from the penetration could influence ISF flow rate. For example, a beveled design makes a linear incision in the stratum corneum, whereas a cone design makes a point defect. Examples of Pressure Plate Designs The design of the pressure plate is critically important to the performance of the ISF collection device. The design determines the pressure distribution in the skin that drives ISF flow, the capillary force that holds the collected fluid, and the degree to which the puncture sites remain open during collection. In the base design, pressure is applied around each of the puncture sites, creating a pressure gradient that drives ISF flow into the puncture sites. Curvatures can be added to the plate to create an additional gradient Attorney Docket No.: STAN-2203WO Stanford No.: S24-200 at the patch level over a larger length scale (Figure 4). This allows for pressure gradient engineering to achieve design goals such as encouraging fluid flow towards the center of the plate or to ensure uniform pressure across the plate by matching the skin curvature. Plate curvature for pressure gradient engineering. Since ISF flow is determined by the 3D distribution of the pressure gradient created, the flow can be controlled by curvatures on the pressure plate. a) Engineering higher pressures around the plate edges drives ISF flow towards the center. b) Matching the skin curvature during pressure application allows the pressure to be more uniformly distributed in applications where uniform collection from each puncture site is desired, such as in the investigation of the spatial distribution of biomarkers. A variety of strategies can be employed to maximize the capillary force utilized to trap the collected fluid, including engineering the geometry of the holes (Figure 2), using surface treatments such as UV exposure or oxygen plasma to increase the hydrophilicity of the surface, and adding a special-grade paper between the plate and the skin to collect the ISF. Capillary force can be engineered by the geometry of the holes in the plate, including their shape, height, and lateral dimension. Lastly, design features can be integrated into the plate such as open cylinders on the skin-facing side to keep the puncture sites open during ISF collection (Figure 3). Cylinders on the skin side of the plate can be inserted into the puncture sites to keep the puncture sites open and to maintain the flow of ISF. Examples of Integrated One-part System The concept of the two-part ISF collection device can be expanded into an integrated design (Figure 5). By integrating lattice microneedles with the pressure plate, one-step ISF collection can be achieved. Regions of the device, including the interior of the base plate and the interior of the lattice microneedles, can be modified to increase hydrophilicity. This will facilitate collection and retention of ISF, particularly for larger ISF volumes. By engineering the surface energies via geometry and surface modifications, both at the microneedle and the plate level, capillary withdrawal of ISF can be maximized. Attorney Docket No.: STAN-2203WO Stanford No.: S24-200 Notwithstanding the appended claims, the disclosure is also defined by the following clauses: 1. A microneedle array patch comprising: a polymeric structure comprising an array of polymeric microneedles configured to puncture the skin of a subject; and a pressure plate comprising an array of holes configured for collecting a biological fluid sample from each skin puncture site by the array of polymeric microneedles. 2. The microneedle array patch according to clause 1, wherein the array of holes of the pressure plate is configured for insertion of the polymeric microneedles therethrough. 3. The microneedle array patch according to any one of clauses 1-2, wherein the pressure plate comprises a planar surface. 4. The microneedle array patch according to any one of clauses 1-2, wherein the pressure plate comprises a concave surface. 5. The microneedle array patch according to any one of clauses 1-2, wherein the pressure plate comprises a convex surface. 6. The microneedle array patch according to any one of clauses 1-5, wherein the pressure plate comprises a surface that matches the skin curvature of the subject. 7. The microneedle array patch according to any one of clauses 1-5, wherein the pressure plate comprises a shape-conforming surface. 8. The microneedle array patch according to any one of clauses 1-7, wherein the surface of the pressure plate further comprises a wall which extends from each of the array of holes. 9. The microneedle array patch according to clause 8, wherein the walls are configured for insertion into each puncture site by the array of polymeric microneedles. 10. The microneedle array patch according to any one of clauses 1-9, wherein the pressure plate comprises a reservoir for the collected biological fluid sample. 11. The microneedle array patch according to any one of clauses 1-10, wherein the pressure plate comprises one or more hydrophilic surfaces. Attorney Docket No.: STAN-2203WO Stanford No.: S24-200 12. The microneedle array patch according to clause 11, wherein one or more of the array of holes comprises a hydrophilic surface. 13. The microneedle array patch according to any one of clauses 1-12, wherein each of the holes of the pressure plate have a circular cross-section. 14. The microneedle array patch according to any one of clauses 1-12, wherein each of the holes of the pressure plate have a triangular cross-section. 15. The microneedle array patch according to any one of clauses 1-12, wherein each of the holes of the pressure plate have a square cross-section. 16. The microneedle array patch according to any one of clauses 1-15, wherein each of the holes of the pressure plate have a width of from 200 µm to 750 µm. 17. The microneedle array patch according to any one of clauses 1-15, wherein each of the holes of the pressure plate have a width of from 300 µm to 675 µm. 18. The microneedle array patch according to any one of clauses 1-17, wherein the pressure plate comprises a height of from 300 µm to 2000 µm. 19. The microneedle array patch according to any one of clauses 1-18, wherein each hole of the pressure plate comprises a volume of from 0.1 µL to 100 µL. 20. The microneedle array patch according to any one of clauses 1-18, wherein each hole of the pressure plate comprises a volume of from 2 µL to 25 µL. 21. The microneedle array patch according to any one of clauses 1-20, wherein the polymeric structure comprising the array of polymeric microneedles is integrated together with the pressure plate. 22. The microneedle array patch according to any one of clauses 1-21, wherein each polymeric microneedle comprises a beveled tip. 23. The microneedle array patch according to any one of clauses 1-22, wherein each polymeric microneedle comprises a lattice structure. 24. The microneedle array patch according to clause 23, wherein the lattice structure comprises 2 or more repeating lattice cell units. 25. The microneedle array patch according to clause 24, wherein the lattice cell unit comprises a lattice shape selected from the group consisting of tetrahedral, Kagome, rhombic, icosahedral, Voronoi and triangular. 26. The microneedle array patch according to any one of clauses 1-25, wherein each polymeric microneedle comprises a width of from 200 µm to 750 µm. Attorney Docket No.: STAN-2203WO Stanford No.: S24-200 27. The microneedle array patch according to any one of clauses 1-26, wherein each polymeric microneedle comprises a length of from 300 µm to 3000 µm. 28. The microneedle array patch according to any one of clauses 1-27, wherein each polymeric microneedle comprises a hollow internal space. 29. The microneedle array patch according to clause 28, wherein one or more of the polymeric microneedles comprises: a tip section comprising a lattice structure; a body section comprising a hollow structure; and a base section comprising a solid structure. 30. The microneedle array patch according to any one of clauses 1-29, wherein the biological fluid sample comprises interstitial fluid. 31. The microneedle array patch according to any one of clauses 1-29, wherein the biological fluid sample comprises dermal fluid. 32. A method comprising: puncturing the skin of a subject with a polymeric structure comprising an array of polymeric microneedles; and collecting a biological fluid sample from each skin puncture site into an array of holes of a pressure plate. 33. The method according to clause 32, wherein the method comprises: positioning the pressure plate on the surface of the skin of the subject; and puncturing the skin surface by inserting the array of polymeric microneedles through the array of holes of the pressure plate. 34. The method according to any one of clauses 32-33, wherein the method comprises retracting the array of microneedles from the skin surface. 35. The method according to clause 34, wherein the method further comprises applying pressure to the pressure plate. 36. The method according to any one of clauses 32-35, wherein the biological fluid sample comprises interstitial fluid. 37. The method according to any one of clauses 32-35, wherein the biological fluid sample comprises dermal fluid. 38. The method according to any one of clauses 32-37, wherein the biological fluid sample is collected at a rate of from 1 µL to 10 µL per minute. Attorney Docket No.: STAN-2203WO Stanford No.: S24-200 39. The method according to clause 38, wherein the biological fluid sample is collected at a rate of from 5 µL to 20 µL in 20 minutes. 40. The method according to any one of clauses 32-39, wherein the pressure plate comprises a planar surface. 41. The method according to any one of clauses 32-39, wherein the pressure plate comprises a concave surface. 42. The method according to any one of clauses 32-39, wherein the pressure plate comprises a convex surface. 43. The method according to any one of clauses 32-42, wherein the pressure plate comprises a surface that matches the skin curvature of the subject. 44. The method according to any one of clauses 32-42, wherein the pressure plate comprises a shape-conforming surface. 45. The method according to any one of clauses 32-44, wherein the surface of the pressure plate further comprises a wall which extends from each of the array of holes. 46. The method according to clause 45, wherein the walls are configured for insertion into each puncture site by the array of polymeric microneedles. 47. The method according to any one of clauses 32-46, wherein the pressure plate comprises a reservoir for the collected biological fluid sample. 48. The method according to any one of clauses 32-47, wherein the pressure plate comprises one or more hydrophilic surfaces. 49. The method according to clause 48, wherein one or more of the array of holes comprises a hydrophilic surface. 50. The method according to any one of clauses 32-49, wherein each of the holes of the pressure plate have a circular cross-section. 51. The method according to any one of clauses 32-50, wherein each of the holes of the pressure plate have a triangular cross-section. 52. The method according to any one of clauses 32-50, wherein each of the holes of the pressure plate have a square cross-section. 53. The method according to any one of clauses 32-52, wherein each of the holes of the pressure plate have a width of from 200 µm to 750 µm. 54. The method according to any one of clauses 32-53, wherein each of the holes of the pressure plate have a width of from 300 µm to 675 µm. Attorney Docket No.: STAN-2203WO Stanford No.: S24-200 55. The method according to any one of clauses 32-54, wherein the pressure plate comprises a height of 300 µm to 2000 µm. 56. The method according to any one of clauses 32-55, wherein each hole of the pressure plate comprises a volume of from 0.1 µL to 100 µL. 57. The method according to any one of clauses 32-56, wherein each hole of the pressure plate comprises a volume of from 2 µL to 25 µL. 58. The method according to any one of clauses 32-57, wherein the polymeric structure comprising the array of polymeric microneedles is integrated together with the pressure plate. 59. The method according to any one of clauses 32-58, wherein each polymeric microneedle comprises a beveled tip. 60. The method according to any one of clauses 32-59, wherein each polymeric microneedle comprises a lattice structure. 61. The method according to clause 60, wherein the lattice structure comprises 2 or more repeating lattice cell units. 62. The method according to clause 61, wherein the lattice cell unit comprises a lattice shape selected from the group consisting of tetrahedral, Kagome, rhombic, icosahedral, Voronoi and triangular. 63. The method according to any one of clauses 32-62, wherein each polymeric microneedle comprises a width of from 200 µm to 750 µm. 64. The method according to any one of clauses 32-63, wherein each polymeric microneedle comprises a length of from 300 µm to 3000 µm. 65. The method according to any one of clauses 32-64, wherein each polymeric microneedle comprises a hollow internal space. 66. The method according to clause 65, wherein one or more of the polymeric microneedles comprises: a tip section comprising a lattice structure; a body section comprising a hollow structure; and a base section comprising a solid structure. 67. A kit comprising: a microneedle array patch comprising: Attorney Docket No.: STAN-2203WO Stanford No.: S24-200 a polymeric structure comprising an array of polymeric microneedles configured to puncture the skin of a subject; and a pressure plate comprising an array of holes configured for collecting a biological fluid sample from each skin puncture site by the array of polymeric microneedles; and instructions for applying the microneedle array patch to a skin surface of a subject. 68. The kit according to clause 67, wherein the kit comprises two or more of the microneedle array patches. 69. The kit according to any one of clauses 67-68, wherein the kit comprises instructions for applying the microneedle array patches to the skin surface of the subject by puncturing the skin surface of the subject by inserting the array of polymeric microneedles through the array of holes of the pressure plate. 70. The kit according to clause 69, wherein the biological fluid sample comprises interstitial fluid. 71. The kit according to clause 69, wherein the biological fluid sample comprises dermal fluid. Although the foregoing invention has been described in some detail by way of illustration and example for purposes of clarity of understanding, it is readily apparent to those of ordinary skill in the art in light of the teachings of this invention that certain changes and modifications may be made thereto without departing from the spirit or scope of the appended claims. Accordingly, the preceding merely illustrates the principles of the invention. It will be appreciated that those skilled in the art will be able to devise various arrangements which, although not explicitly described or shown herein, embody the principles of the invention and are included within its spirit and scope. Furthermore, all examples and conditional language recited herein are principally intended to aid the reader in understanding the principles of the invention and the concepts contributed by the inventors to furthering the art, and are to be construed as being without limitation to such specifically recited examples and conditions. Moreover, all statements herein reciting principles, aspects, and embodiments of the invention as well as specific examples Attorney Docket No.: STAN-2203WO Stanford No.: S24-200 thereof, are intended to encompass both structural and functional equivalents thereof. Additionally, it is intended that such equivalents include both currently known equivalents and equivalents developed in the future, i.e., any elements developed that perform the same function, regardless of structure. Moreover, nothing disclosed herein is intended to be dedicated to the public regardless of whether such disclosure is explicitly recited in the claims. The scope of the present invention, therefore, is not intended to be limited to the exemplary embodiments shown and described herein. Rather, the scope and spirit of present invention is embodied by the appended claims. In the claims, 35 U.S.C. §112(f) or 35 U.S.C. §112(6) is expressly defined as being invoked for a limitation in the claim only when the exact phrase "means for" or the exact phrase "step for" is recited at the beginning of such limitation in the claim; if such exact phrase is not used in a limitation in the claim, then 35 U.S.C. § 112 (f) or 35 U.S.C. §112(6) is not invoked.
Claims
Attorney Docket No.: STAN-2203WO Stanford No.: S24-200 What is claimed is:
1. A microneedle array patch comprising: a polymeric structure comprising an array of polymeric microneedles configured to puncture the skin of a subject; and a pressure plate comprising an array of holes configured for collecting a biological fluid sample from each skin puncture site by the array of polymeric microneedles.
2. The microneedle array patch according to claim 1, wherein the array of holes of the pressure plate is configured for insertion of the polymeric microneedles therethrough.
3. The microneedle array patch according to any one of claims 1-2, wherein the pressure plate comprises a planar surface, a concave surface, a convex surface, a shape-conforming surface or a surface that matches the skin curvature of the subject.
4. The microneedle array patch according to any one of claims 1-3, wherein the surface of the pressure plate further comprises a wall which extends from each of the array of holes and the walls are configured for insertion into each puncture site by the array of polymeric microneedles.
5. The microneedle array patch according to any one of claims 1-4, wherein the pressure plate comprises a reservoir for the collected biological fluid sample.
6. The microneedle array patch according to any one of claims 1-5, wherein the pressure plate comprises one or more hydrophilic surfaces and wherein one or more of the array of holes comprises a hydrophilic surface.
7. The microneedle array patch according to any one of claims 1-6, wherein the holes of the pressure plate have one or more of: a circular cross-section, a triangular cross-section, a square cross-section or a combination thereof.Attorney Docket No.: STAN-2203WO Stanford No.: S24-200 8. The microneedle array patch according to any one of claims 1-7, wherein each of the holes of the pressure plate have: a width of from 200 µm to 750 µm; a height of from 300 µm to 2000 µm; and a volume of from 0.1 µL to 100 µL.
9. The microneedle array patch according to any one of claims 1-8, wherein the polymeric structure comprising the array of polymeric microneedles is integrated together with the pressure plate.
10. The microneedle array patch according to any one of claims 1-9, wherein each polymeric microneedle comprises a lattice structure.
11. A method comprising: puncturing the skin of a subject with a polymeric structure comprising an array of polymeric microneedles; and collecting a biological fluid sample from each skin puncture site into an array of holes of a pressure plate.
12. The method according to claim 11, wherein the method comprises: positioning the pressure plate on the surface of the skin of the subject; and puncturing the skin surface by inserting the array of polymeric microneedles through the array of holes of the pressure plate.
13. The method according to any one of claims 11-12, wherein the biological fluid sample comprises interstitial fluid or dermal fluid.
14. The method according to any one of claims 11-13, wherein the biological fluid sample is collected at a rate of from 1 µL to 10 µL per minute.
15. A kit comprising: a microneedle array patch comprising:Attorney Docket No.: STAN-2203WO Stanford No.: S24-200 a polymeric structure comprising an array of polymeric microneedles configured to puncture the skin of a subject; and a pressure plate comprising an array of holes configured for collecting a biological fluid sample from each skin puncture site by the array of polymeric microneedles; and instructions for applying the microneedle array patch to a skin surface of a subject.
Citation Information
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